The EAGeR trial was a multi-center, block-randomized, double-blind, placebo-controlled trial conducted across four medical centers in the U.S. from 2007 to 2012. A total of 1228 women ages 18-40 years with up to two documented prior miscarriages and who planned to become pregnant again were randomized for this trial, making the EAGeR trial the largest preconception trial of LDA. Each woman was randomly assigned to 81 mg aspirin daily or placebo beginning prior to conception and continued to 36 weeks gestation in women achieving pregnancy. Participants were block randomized by study center and eligibility stratum, defined based on specific eligibility qualifications: 1) original stratum, women with exactly one documented pregnancy loss <20 weeks gestation during the preceding 12 months; and 2) expanded stratum, women not meeting all criteria for the original stratum, and having 1 or 2 prior pregnancy losses of any gestational age at any time in the past. Participants attended two study visits per menstrual cycle for the first two cycles attempting pregnancy and once per cycle thereafter, which included spot urine and blood sample collection. Follow-up ended after six menstrual cycles attempting pregnancy or, in women becoming pregnant, throughout pregnancy. EAGeR recruitment started in June 2007 and ended in July 2011. Since the completion of EAGeR, Dr. Schisterman and the EAGeR team have completed analysis of the primary (live birth) and secondary trial outcomes (pregnancy rates and pregnancy outcomes, including losses), and examined several ancillary study questions. The primary outcomes of the EAGeR trial were published in 2014 (Schisterman et al. Lancet 2014), with additional findings regarding secondary outcomes published in 2015 and 2016. Overall, we found that a daily low dose of aspirin does not appear to prevent subsequent pregnancy loss among women with a history of one or two prior pregnancy losses(Schisterman et al. Lancet 2014; Mumford et al. Human Reproduction 2016). In addition, we found that preconception low-dose aspirin was well tolerated by women trying to conceive, and among women who became pregnant, and that rates of maternal, fetal, and neonatal complications were similar between treatment arms (Ahrens et al. Obstetrics and Gynecology 2016). We have also evaluated the utility of routine anti-Mullerian hormone (AMH) testing for prediction of pregnancy loss and preconception counseling in young, fecund women and have found that AMH levels were not associated with pregnancy loss (Zarek et al. Fertility and Sterility 2016). Thus, our data do not support routine AMH testing in fertile women. Moreover, our data also suggest that the current recommendations for delaying pregnancy attempt after an early loss may be unwarranted (Schliep et al. Obstetrics and Gynecology 2016). We also evaluated the role of subclinical hypothyroidism and antithyroid antibodies and found no associations with time to pregnancy and pregnancy loss, which are reassuring findings for women with subclinical hypothyroidism (Plowden et al. Journal of Clinical Endocrinology and Metabolism 2016). Importantly, we found that nausea and vomiting were common very early in pregnancy and were associated with a reduced risk for pregnancy loss (Hinkle et al. JAMA Internal Medicine 2016). These findings overcome prior analytic and design limitations and represent the most definitive data available to date indicating the protective association of nausea and vomiting in early pregnancy and the risk for pregnancy loss. The team intends to build upon its current findings from the EAGeR Trial to fill critical research gaps in its quest to answer important public health questions for women of reproductive age.
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